Identification of platelet function defects by multi-parameter assessment of thrombus formation

被引：190

作者：

de Witt, Susanne M. ^{[1
]}

Swieringa, Frauke ^{[1
]}

Cavill, Rachel ^{[2
]}

Lamers, Moniek M. E. ^{[1
]}

van Kruchten, Roger ^{[1
]}

Mastenbroek, Tom ^{[1
]}

Baaten, Constance ^{[1
]}

Coort, Susan ^{[3
]}

Pugh, Nicholas ^{[4
]}

Schulz, Ansgar ^{[5
]}

Scharrer, Inge ^{[6
]}

Jurk, Kerstin ^{[6
]}

Zieger, Barbara ^{[7
]}

Clemetson, Kenneth J. ^{[8
]}

Farndale, Richard W. ^{[9
]}

Heemskerk, Johan W. M. ^{[1
]}

Cosemans, Judith M. E. M. ^{[1
]}

机构：

[1] Maastricht Univ, Cardiovasc Res Inst Maastricht CARIM, Dept Biochem, NL-6229 ER Maastricht, Netherlands

[2] Maastricht Univ, Dept Toxicogen, NL-6229 ER Maastricht, Netherlands

[3] Maastricht Univ, Dept Bioinformat, NL-6229 ER Maastricht, Netherlands

[4] Anglia Ruskin Univ, Cambridge CB1 1PT, England

[5] Univ Klin Kinder & Jugendmed, Univ Clin Ulm, Pediat Ctr, D-89075 Ulm, Germany

[6] Johannes Gutenberg Univ Mainz, Univ Med Johannes Gutenberg, CTH, D-55131 Mainz, Germany

[7] Univ Med Ctr Freiburg, Dept Pediat & Adolescent Med, D-79106 Freiburg, Germany

[8] Univ Bern, Inselspital, Dept Haematol, CH-3010 Bern, Switzerland

[9] Univ Cambridge, Dept Biochem, Cambridge CB2 1QW, England

来源：

NATURE COMMUNICATIONS | 2014年 / 5卷

基金：

英国惠康基金;

关键词：

VON-WILLEBRAND-FACTOR; AFFINITY BINDING; COLLAGEN; ADHESION; FLOW; ACTIVATION; FIBRINOGEN; RECEPTOR; SITE; SHEAR;

D O I：

10.1038/ncomms5257

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

Assays measuring platelet aggregation (thrombus formation) at arterial shear rate mostly use collagen as only platelet-adhesive surface. Here we report a multi-surface and multi-parameter flow assay to characterize thrombus formation in whole blood from healthy subjects and patients with platelet function deficiencies. A systematic comparison is made of 52 adhesive surfaces with components activating the main platelet-adhesive receptors, and of eight output parameters reflecting distinct stages of thrombus formation. Three types of thrombus formation can be identified with a predicted hierarchy of the following receptors: glycoprotein (GP) VI, C-type lectin-like receptor-2 (CLEC-2) > GPIb > alpha(6)beta(1), alpha(IIb)beta(3)>alpha(2)beta(1)>CD36, alpha(5)beta(3), alpha(v)beta(3). Application with patient blood reveals distinct abnormalities in thrombus formation in patients with severe combined immune deficiency, Glanzmann's thrombasthenia, Hermansky-Pudlak syndrome, May-Hegglin anomaly or grey platelet syndrome. We suggest this test may be useful for the diagnosis of patients with suspected bleeding disorders or a pro-thrombotic tendency.

引用

页数：13

共 53 条

[1]

VITRONECTIN BINDS TO ACTIVATED HUMAN PLATELETS AND PLAYS A ROLE IN PLATELET-AGGREGATION [J].